TY - JOUR
T1 - 15-Hydroxy-eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator-activated receptor gamma-dependent pathway
AU - Chen, George G.
AU - Xu, Hu
AU - Lee, Janet F.Y.
AU - Subramaniam, Malayannan
AU - Leung, Ka L.
AU - Wang, Su H.
AU - Chan, Ursula P.F.
AU - Spelsberg, Thomas C.
PY - 2003/12/10
Y1 - 2003/12/10
N2 - Peroxisome proliferator-activated receptor gamma (PPARγ) inhibits cell growth via promoting apoptosis. Human colorectal cancer tissues had abundant PPARγ but the incidence of apoptosis was very low, suggesting a defect in the PPARγ pathway. Here, we found that 15-hydroxy-eicosatetraenoic acid (15S-HETE), an endogenous ligand for PPARγ, was significantly decreased in the serum of patients with colorectal cancer. Treatment of colon cancer cells with 15S-HETE inhibited cell proliferation and induced apoptosis, which was preceded by an increase in TGF-β-inducible early gene (TIEG) and a decrease in Bcl-2. The action of 15S-HETE could be blocked when PPARγ was suppressed. Overexpression of Bcl-2 prevented the apoptosis. The levels of TIEG and 15-lipoxygenase (15-LOX), the enzyme responsible for 15S-HETE production, was decreased in colorectal cancer. Therefore, colorectal cancer is associated with decreased 15S-HETE. Treatment of colon cancer cells with 15S-HETE inhibits cell proliferation and induces apoptosis in a PPARγ-dependent pathway involving augmentation of TIEG and reduction of Bcl-2 expression.
AB - Peroxisome proliferator-activated receptor gamma (PPARγ) inhibits cell growth via promoting apoptosis. Human colorectal cancer tissues had abundant PPARγ but the incidence of apoptosis was very low, suggesting a defect in the PPARγ pathway. Here, we found that 15-hydroxy-eicosatetraenoic acid (15S-HETE), an endogenous ligand for PPARγ, was significantly decreased in the serum of patients with colorectal cancer. Treatment of colon cancer cells with 15S-HETE inhibited cell proliferation and induced apoptosis, which was preceded by an increase in TGF-β-inducible early gene (TIEG) and a decrease in Bcl-2. The action of 15S-HETE could be blocked when PPARγ was suppressed. Overexpression of Bcl-2 prevented the apoptosis. The levels of TIEG and 15-lipoxygenase (15-LOX), the enzyme responsible for 15S-HETE production, was decreased in colorectal cancer. Therefore, colorectal cancer is associated with decreased 15S-HETE. Treatment of colon cancer cells with 15S-HETE inhibits cell proliferation and induces apoptosis in a PPARγ-dependent pathway involving augmentation of TIEG and reduction of Bcl-2 expression.
KW - 15-hydroxy-eicosatetraenoic acid
KW - 15-lipoxygenase
KW - Colorectal carcinoma
KW - Peroxisome proliferator-activated receptor gamma
KW - TGF-β-inducible early gene and Bcl-2
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UR - http://www.scopus.com/inward/citedby.url?scp=0242363581&partnerID=8YFLogxK
U2 - 10.1002/ijc.11447
DO - 10.1002/ijc.11447
M3 - Article
C2 - 14566836
AN - SCOPUS:0242363581
SN - 0020-7136
VL - 107
SP - 837
EP - 843
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 5
ER -